Abstract: Micro-arrays provide a high-throughput platform for various key studies in functional-genomics, proteomics, epigenetics, medical-diagnostics and even tissue-engineering. Together with advanced biochemical detection, imaging and bioinformatics technologies, it is now possible to cost-effectively monitor the expression behavior of genes, proteins or other biomarkers, as well as screening the genome and proteome content of various cell lines, on-chip drug profiling or even detection of single-nucleotide-polymorphism. Therefore, micro-array technologies provide a vital platform for performing high-throughput screening experiments that shed light on our understanding of cellular, genomic, and proteomic processes occurring at the nano-scale. In this proposal, we aim to create the next-generation of micro-array technologies to achieve an unprecedented mega-throughput, i.e., label-free imaging of millions of DNA/protein microspots would be feasible per second. We term the broad-umbrella of these revolutionary technologies as Nano-plasmonic LUCAS. Specifically, we aim achieve a throughput of >120 cm2/second or >4.5 million spots/second for highlysensitive and label-free imaging of DNA/protein micro-arrays, which constitutes a speed improvement of >3 orders-of-magnitude when compared to the state-of-the-art. Label-free imaging is especially important not to perturb the natural bio-chemical, physical and structural properties of the original molecule-of-interest. It also makes the measurements much more quantitative, significantly improving the data quality;eliminates inconvenient labeling steps which further reduces the cost;and avoids cross-reactivity issues among secondary-probes which can significantly improve the detection of weak or transitional molecular interactions. This mega-throughput capability will revolutionize the speed of progress that is taken in proteomics/genetics research by orders-of-magnitude that could eventually lead to the development of improved strategies/therapies for combating previously intractable bio-medical problems and various diseases including cancer. Furthermore, the Nano-plasmonic LUCAS platform does not require any lenses, microscope-objectives or other bulk optical components, and therefore offers an extremely compact on-chip platform that can easily be merged with micro-fluidic systems to permit point-of-care operation. Public Health Relevance: In this high-risk high pay-off proposal, we aim to create the next generation of micro-array technologies to revolutionize the speed of progress that is taken in proteomics and genetics research by orders of magnitude that could eventually lead to the development of improved strategies and therapies for combating previously intractable bio-medical problems and various diseases including cancer.